Chlorinated hydrocarbons are used extensively in industrial settings. While these chemicals can produce liver and kidney injury in employees exposed to toxic concentrations, safe working conditions have been established for these solvents when they are employed singly. However, other common industrial solvents have been shown to enhance the hepato- and nephrotoxic properties of certain haloalkane solvents. Thus, normally safe concentrations of a haloalkane may become hazardous due to the presence of an additional chemical agent in the working environment. Animal models have been developed which have a certain predictive value for determining the ability of solvent mixtures to interact and produce a potentiated hepatotoxic response. However, similar models, capable of predicting the potentiation of haloalkane-induced nephrotoxicity, do not exist. Recently, the applicant has demonstrated that three ketonic solvents can interact with chloroform, a representative haloalkane, to produce a potentiated nephrotoxic response in rats. Based on this observation, the project is designed to: (1) determine if ketonic solvents, as a class, are capable of potentiating haloalkane-induced nephrotoxicity; and, (2) determine the mechanism(s) by which the nephrotoxicity of chloroform was potentiated by ketonic solvents. These objectives will be fulfilled by performing a pharmacodynamic analysis of the potentiation phenomenon produced by five representative ketones and by analyzing the effects of ketones on the renal chloroform biotransformation capacity. In addition, the ability of ketonic solvents to alter the nephrotoxic properties of other haloalkanes will be determined. Ultimately, it is hoped that an animal model capable of predicting the ability of chemicals to interact and produce a potentiated nephrotoxic response will be developed.